The present study investigated possible clinical differences between bipolar patients with and without manic or hypomanic switch during
antidepressant (AD) treatment. The authors undertook a retrospective assessment of 169 individuals affected by
bipolar disorder type I (BP I: n=96) and II (BP II: n=73) who experienced at least one manic or
hypomanic episode following depression without any interposed normothymic period ("manic switch") during AD
therapy. They were compared with a sex, age (+/-5 years), and ethnicity-matched group of 247 subjects, randomly selected from our pool of bipolar subjects who have never had manic switches. Only 2 of the 169 patients had had spontaneous switches before the AD-related one. Switched subjects were marginally older (t=-2.65, df=414, P=.008) compared to not switched and less frequently delusional (chi2=13.86, P=.0002). Polarity of the onset episode was more frequently depressive in switched patients (chi2=21.93, P=.00002), which had also less previous
manic episodes than not switched (t=3.44, df=332, P=.0006). Those differences were more pronounced in the BP I subsample. Switched patients were more frequently BP I (chi2=29.66; P<.00001). Maintenance with mood stabilizers appears to be a strong protective factor; in fact, of the 124 individuals undertaking a mood stabilizer
therapy, 21 had a switch and 103 had no switches (chi2=41.10, P<.000001). In conclusion, some clinical variables, such as the number of
manic episodes, the presence of delusions, the polarity of onset episode, and the mood-stabilizing treatment, may be involved in AD-related switches. Further studies are required to investigate the causal relationships between those factors.